This invention relates to procedures and to devices for treating cardiac tissue by forming lesions in that tissue using photodynamic therapy techniques. In particular, the procedure is valuable for rectifying various cardiac arrhythymias with those so-formed lesions. Central to this procedure is the delivery of light to the desired lesion site in cooperation with delivery of a photodynamic drug to that site. The invention also relates to devices, particularly catheters, that are suitable for delivering the light for forming those lesions.
Many abnormal medical conditions in humans and other mammals have been associated with disease and other aberrations along the lining or walls of blood vessels. Treatment of such abnormal wall conditions has included various medical device technologies that deliver various forms of energy to specific regions of vascular wall tissue.
For instance, atherosclerosis, a vascular disease characterized by abnormal deposits upon vessel walls or the thickening of those walls, is an example of an abnormal wall condition. The dangers related to flow blockages or functional occlusions resulting from the disease have made atherosclerosis the focus of many medical devices. Such devices are often categorized by structure and tissue treatment mechanism. The categories include direct contact electrode devices, resistance heating devices, light transmission devices, light-to-heat conversion devices, hot fluid devices, and radio frequency (RF) heated devices.
The first category includes a variety of contact electrode devices. For instance, U.S. Pat. No. 4,998,933, to Eggers et al, describes a catheter for thermal angioplasty using a heated electrode in direct contact with surrounding tissue or plaque deposits. The heated electrode serves to treat the diseased lumen walls. U.S. Pat. No. 4,676,258, to Inokuchi et al, and U.S. Pat. No. 4,807,620, to Strul et al, disclose devices designed to treat surrounding tissues using heat generated by two electrodes within the device and an RF power source.
U.S. Pat. No. 4,672,962, to Hershenson, and U.S. Pat. No. 5,035,694, to Kasprzyk et al, disclose devices which may be categorized as resistance heating probes. In each of these devices, current flowing through a conductive material at the end of the device provides heat that is transmitted to surrounding tissues for treatment of atherosclerosis and other diseases. Current is transmitted in each of these devices by electrically conductive materials. In contrast, U.S. Pat. No. 5,226,430, to Spears et al, discloses a device which uses light transmitting fiber to transmit energy to a heat generating element at the tip of the device. That heat generating element in turn transmits heat energy to a surrounding balloon structure which is in contact with surrounding tissue. Similarly, U.S. Pat. No. 4,790,311, to Ruiz, discloses an angioplasty catheter system having heat generating electrode at the tip of the device that is heated using RF energy. This device may be categorized as an RF heated device.
U.S. Pat. Nos. 5,190,540 and 5,292,321, to Lee, describe hot fluid-containing devices. Lee ""540 shows a balloon catheter designed for remodeling a body lumen. This catheter uses a multilumen shaft that delivers a heated fluid to an expandable balloon. The expanded balloon heats the tissue that is in contact with the expanded balloon. Lee ""321 shows a somewhat similar device. However, the expandable balloon is instead filled with a selected thermoplastic material that becomes softer and more compliant when heated by a heating element.
Diseased or structurally damaged blood vessels often involve various abnormal wall conditions. The inducement of thrombosis and control of hemorrhaging within such vessels have been the focus of several devices that use catheter-based heat sources for cauterizing damaged tissues. U.S. Pat. No. 4,449,528, to Auth et al, discloses a thermal cautery probe designed for heating specific layers of tissue without producing deep tissue damage. The mechanism of heat generation in this device is a resistive coil within the cautery probe that is electrically connected to a power source. U.S. Pat. No. 4,662,368, to Hussein et al, discloses a device designed for localized heat application within a lumen; In this device, energy in the form of light is delivered to the tip of the device for heat generation, by a flexible fiber. Heat from an element that converts light energy to heat energy passes to the adjacent tissue.
Although there are a variety of devices that deliver energy to vascular lumena, none of them deliver the energy in the form of light which cooperatively forms lesions in cardiac tissue using photodynamic chemicals to treat that cardiac tissue and to prevent various forms of fibrillation.
Cardiac arrhythmias, and atrial fibrillation in particular, are common, dangerous medical ailments, particularly in the aging population. In patients with normal sinus rhythm, the heart, which is made up of atrial, ventricular, and excitatory conduction tissue, is electrically excited to beat in a synchronous, patterned fashion. In patients with cardiac arrhythmia, regions of cardiac tissue do not follow the synchronous beating cycle associated with normally conductive tissue in patients with sinus rhythm. Instead, the abnormal regions of cardiac tissue aberrantly conduct to adjacent tissue, thereby disrupting the cardiac cycle into an asynchronous cardiac rhythm. Such abnormal conduction generally occurs at various, specific regions of the heart, for example: in the region of the sino-atrial (SA) node, along the conduction pathways of the atrioventricular (AV) node and the Bundle of His, or in the cardiac muscle tissue forming the walls of the ventricular and atrial cardiac chambers.
Cardiac arrhythmias, including atrial arrhythmia, may be of a multiwavelet re-entrant type, characterized by multiple asynchronous loops of electrical impulses that are scattered about the atrial chamber. These arrhythmias are often self propagating. Cardiac arrhythmias may also have a focal origin, such as when an isolated region of tissue in an atrium fires autonomously in a rapid, repetitive fashion. Cardiac arrhythmias, including atrial fibrillation, may be detected using the global technique of an electrocardiogram (EKG). More sensitive procedures of mapping the specific conduction along the cardiac chambers have also been disclosed, such as for example in U.S. Pat. No. 4,641,649 to Walinsky et al and WO 96/32897 to Desai.
A variety of clinical conditions may result from the irregular cardiac function and resulting hemodynamic abnormalities associated with atrial fibrillation, including stroke, heart failure, and other thromboembolic events. Atrial fibrillation is believed to be a significant cause of cerebral stroke; the abnormal hemodynamics in the left atrium caused by the fibrillatory wall motion precipitate the formation of thrombus within the atrial chamber. A thromboembolism is ultimately thrown off into the left ventricle, which then pumps the embolism into the cerebral circulation causing a stroke. For these reasons, there are a number of procedures for treating atrial arrhythmias.
Conventional Atrial Arrhythmia Treatments
There are several pharmacological approaches intended to remedy or otherwise treat atrial arrhythrnias. See. for example, U.S. Pat. No. 4,673,563, to Beme et al; U.S. Pat. No. 4,569,801, to Molloy et al; and Hindricks, et al in xe2x80x9cCurrent Management of Arrhythmiasxe2x80x9d (1991). However, such pharmacological solutions are not always effective and may in some cases result in proarrhythmia and long term inefficacy.
Several surgical approaches have been developed to treat atrial fibrillation. One example is known as the xe2x80x9cmaze procedure,xe2x80x9d as is disclosed by Cox, J. L. et al in xe2x80x9cThe surgical treatment of atrial fibrillation. I. Summaryxe2x80x9d Thoracic and Cardiovascular Surgery 101(3), pp. 402-405 (1991); and also by Cox, J. L. in xe2x80x9cThe surgical treatment of atrial fibrillation. IV. Surgical Techniquexe2x80x9d, Thoracic and Cardiovascular Surgery 101(4), pp. 584-592 (1991). In general, the xe2x80x9cmazexe2x80x9d procedure is designed to relieve atrial arrhythmia by restoring effective atrial systole and sinus node control via a specific pattern of incisions in the tissue wall. Early on, the xe2x80x9cmazexe2x80x9d procedure included surgical incisions in both the right and the left atrial chambers. However, more recent reports predict that the surgical xe2x80x9cmazexe2x80x9d procedure may be effective when performed only in the left atrium. See, Sueda et al, xe2x80x9cSimple Left Atrial Procedure for Chronic Atrial Fibrillation Associated With Mitral Valve Diseasexe2x80x9d (1996).
The xe2x80x9cmaze procedurexe2x80x9d as surgically performed in the left atrium generally includes forming vertical incisions from the two superior pulmonary veins and terminating in the region of the mitral valve annulus, traversing the inferior pulmonary veins en route. An additional horizontal incision also connects the superior ends of the two vertical incisions. The atrial wall region bordered by the pulmonary vein ostia is therefore isolated from the other atrial tissue. In this way, the mechanical sectioning of atrial tissue eliminates the precipitating conduction to the atrial arrhythmia by creating conduction blocks within the aberrant electrical conduction pathways.
Although the xe2x80x9cmazexe2x80x9d procedure is generally effective, it is a highly invasive procedure. Nevertheless, the procedures have provided a guiding principle for alleviating arrhythmia: the mechanical isolation of faulty cardiac tissue often prevents atrial arrhythmia, and particularly atrial fibrillation caused by perpetually wandering reentrant wavelets or focal regions of arrhythmogenic conduction.
Modern Catheter Treatments for Atrial Arrhythmia
Success with surgical interventions through atrial segmentation, particularly with regard to the surgical xe2x80x9cmazexe2x80x9d procedure just described, has caused others to develop less invasive catheter-based approaches to treat atrial fibrillation through cardiac tissue ablation. Examples of such catheter-based devices and treatment methods have generally targeted atrial segmentation with ablation catheter devices and methods adapted to form linear or curvilinear lesions in the wall tissue which defines the atrial chambers, such as are disclosed in the following: U.S. Pat. No. 5,617,854, to Munsif; U.S. Pat. No. 4,898,591, to Jang et al; U.S. Pat. No. 5,487,385, to Avitall; and U.S. Pat. No. 5,582,609 to Swanson.
Additional examples of catheter-based tissue ablation in performing less-invasive cardiac chamber segmentation procedures are also disclosed in the following articles: xe2x80x9cPhysics and Engineering of Transcatheter Tissue Ablationxe2x80x9d, Avitall et al., Journal of American College of Cardiology, Volume 22, No. 3:921-932 (1993); and xe2x80x9cRight and Left Atrial Radiofrequency Catheter Therapy of Paroxysmal Atrial Fibrillation,xe2x80x9d Haissaguerre, et al., Journal of Cardiovascular Electrophysiology 7(12), pp. 1132-1144 (1996).
Furthermore, various energy delivery modalities (microwave, laser, and more commonly, RF) is used to create conduction blocks (atrial wall lesions) along the cardiac tissue wall. See, WO 93/120767, to Stem et al; U.S. Pat. No. 5,104,393, to Isner et al; and U.S. Pat. No. 5,575,766, to Swartz et al.
Additionally, ablation catheter devices and methods have also been used to ablate arrhythmogenic tissue of the left-sided accessory pathways, such as those associated with the Wolff-Parkinson-White syndrome, through the wall of an adjacent region along the coronary sinus.
For example, Fram et al, in xe2x80x9cFeasibility of RF Powered Thermal Balloon Ablation of Atrioventricular Bypass Tracts via the Coronary Sinus: In vivo Canine Studies,xe2x80x9d PACE, Vol. 18, p 1518-1530 (1995), discloses attempted thermal ablation of left-sided accessory pathways in dogs using a balloon which is heated with bipolar radiofrequency electrodes positioned within the balloon. Fram et al suggests that the lesion depth of some population groups may be sufficient to treat patients with Wolff-Parkinson-White syndrome.
Additional examples of cardiac tissue ablation from the region of the coronary sinus for the purpose of treating particular types of cardiac arrhythmias are disclosed in: xe2x80x9cLong-term effects of percutaneous laser balloon ablation from the canine coronary sinusxe2x80x9d, Schuger CD et al., Circulation (1992) 86:947-954; and xe2x80x9cPercutaneous laser balloon coagulation of accessory pathwaysxe2x80x9d, McMath L P et al., Diagn. Ther. Cardiovasc. Interven. 1991; 1425:165-171.
Focal Arrhythmias Originating from Pulmonary Veins
Atrial fibrillation may be focal in nature, caused by the rapid and repetitive firing of an isolated center within the atrial cardiac muscle tissue. These foci, defined by regions exhibiting a concentric pattern of electrical activation, may act either to trigger atrial fibrillation or to sustain the fibrillation. Some studies have suggested that focal arrhythmia often originates from a tissue region along the pulmonary veins of the left atrium, and even more particularly in the superior pulmonary veins.
Less-invasive percutaneous catheter ablation techniques have been disclosed which use end-electrode catheter designs with the intention of ablating and thereby treating focal arrhythmias in the pulmonary veins. These ablation procedures are typically characterized by the incremental application of electrical energy to the tissue to form focal lesions designed to interrupt the inappropriate conduction pathways.
One example of a focal ablation method intended to destroy and thereby treat focal arrhythmia originating from a pulmonary vein is disclosed by Haissaguerre et al, xe2x80x9cRight and Left Atrial Radiofrequency Catheter Therapy of Paroxysmal Atrial Fibrillation,xe2x80x9d Journal of Cardiovascular Electrophysiology 7(12), pp. 1132-1144 (1996). Haissaguerre et al discloses radiofrequency catheter ablation of drug-refractory paroxysmal atrial fibrillation using linear atrial lesions complemented by focal ablation targeted at arrhythrnogenic foci. The site of the arrhythmogenic foci were generally located just inside the superior pulmonary vein.
In another focal ablation example, Jais et al. in xe2x80x9cA focal source of atrial fibrillation treated by discrete radiofrequency ablationxe2x80x9d Circulation 95:572-576 (1997) discusses the use of an RF ablative technique to patients with paroxysmal arrhythmias originating from focal sources variously in both the right and left atria.
None of the cited references discloses a procedure or assembly for creating lesions in cardiac tissue using a light source in cooperation with photoactivatable chemical compounds to form lesions or conduction blocks about focal arrhythmias.
Central to the invention disclosed here is the use of photodynamic therapy (PDT) techniques to create lesions having the same function as those discussed just above. The inventive methods are significantly less invasive; specifically, the lesions may be created without surgery, without the use of any cardiac bypass procedures, and without the use of heat.
There are a variety of medical procedures requiring administration of light or irradiated energy to a patient within the body. One such example is the use of a light activated compound selectively to kill target cells in a patient; as noted above, such therapy is often termed photodynamic therapy (xe2x80x9cPDTxe2x80x9d). In such PDT methods, a light-activated drug is injected into a patient and a targeted light source is used selectively to activate the drug. When activated by light of a proper wavelength, the light-activated drug produces a toxic, often cytotoxic, agent that mediates the destruction of the surrounding cells or tissue.
Currently, the major application of PDT is for the destruction of malignant cell masses. PDT has been used effectively in the treatment of a variety of human tumors and precancerous conditions including basal and squamous cells, skin cancers, breast cancer, metastatic skin cancers, brain tumors, head and neck cancers, stomach cancers, and female genital tract malignancy, cancers and precancerous conditions of the esophagus such as Barrett""s esophagus. A review of the history and progress of PDT is provided by Marcus, S. Photodynamic Therapy of Human Cancer: Clinical Status, Potential, and Needs. In Gomer, C. J. (ed.); xe2x80x9cFuture Directions and Applications in Photodynamic Therapy.xe2x80x9d Bellingham, W. A. SPIE Optical Engineering Press (1990) pp 5-56. Specific applications of PDT are provided by Overholt et al., Sem. Surg. Oncol. 11:1-5 (1995).
The use of various porphyrin compounds as the photoactivated compounds in such treatments is known. These treatments are often tumor-selective in that selected porphyrin compounds accumulate at higher concentrations in tumor tissue than in normal tissue.
In general, the PDT procedure involves administration of a sensitizer compound (such as the porphyrin derivatives) to the target tissue and a subsequent step involving the application of light to that tissue. The PDT procedures function selectively to eradicate diseased tissue in the immediate area of the light source by generating singlet oxygen and activated molecules which damage tissue in that immediate area. Selectivity is attained through the preferential retention of the photosensitizer in rapidly metabolizing tissue such as tumors (Kessel, David, xe2x80x9cTumor Localization and Photosensitization by Derivatives of Hematoporphyrin. A Reviewxe2x80x9d IEEE J. QUANTUM ELECTRON., QE 23(10): 1718-20 (1987)); virally infected cells (J. Chapman et al, xe2x80x9cInactivation of Viruses in Red Cell Concentrates with the Photo Sensitizer Benzoporphyrin Derivative (BPD)xe2x80x9d, TRANSFUSION 31(suppl): 47S Abstract S172, (1991) and J. North et al., xe2x80x9cViral Inactivation in Blood and Red Cell Concentrates with Benzoporphyrin Derivativexe2x80x9d, Blood Cells, 18: 129-140 (1992)); leukaemic cells (C. H. Jamieson, xe2x80x9cPreferential Uptake of Benzoporphyrin Derivative by Leukaemic versus Normal Cellsxe2x80x9d, Leuk. Res. (England) 1990, 14 (3), pp 209-210); psoriatic plaque (M. W. Rems et al, xe2x80x9cResponse of Psoriasis to Red Laser Light (630 nm) Following Systemic Injection of Hematoporphyrin Derivativexe2x80x9d, Lasers Surg Med. 1984, 4(1) pp 73-77); and atherosclerotic plaque (S. Andersson-Engels et al, xe2x80x9cFluorescence Diagnosis and Photochemical Treatment of Diseased Tissue Using Lasers: Part IIxe2x80x9d, Anal. Chem. 62(1), 19A-27A (1990). The activation of the photosensitizer by light occurs only at the site at which the light is present. Obviously, the photo-sensitizer-mediated destruction of tissue occurs only at the desired treatment site. The non-activated photosensitizer is substantially nontoxic and will eventually be cleared from the body.
In a typical PDT treatment, PHOTOFRIN.RTM. porfimer sodium, BPD, or BPD-MA is injected into a patient. See, for instance, Ho et al., xe2x80x9cActivity and Physicochemical Properties of PHOTOFRIN.RTM.xe2x80x9d, Photochemistry and Photobiology, 54(1), pp 83-87 (1991); U.S. Pat. No. 4,866,168, to Dougherty et al. An appropriate dose is, e.g., 0.255-2.5 mg/kg of body weight, depending upon the diseased tissue and the choice of photosensitizer. At an appropriate time after photosensitizer administration, the diseased tissue or site is illuminated with a light source at an appropriate wavelength (630 nm for PHOTOFRIN.RTM. and 690 nm for BPD) to activate the photosensitizer. The light-activated drug induces the formation of singlet oxygen and free radicals which damage the surrounding tissue. Both the diseased tissue and the vasculature feeding it are affected and the unwanted tissue is either directly destroyed or starved of oxygen and nutrients due to the occlusion of blood vessels. After the completion of the PDT, the treated tissue becomes necrotic and will either debride naturally or be debrided by the clinician.
Hematoporphyrin and PHOTOFRIN.RTM. have absorption spectra in the neighborhood of 630 nm. The absorption spectra of much blood and tissue is also in the same general spectral region. Consequently, much of the energy impinging upon the treated tissue is absorbed in the tissue itself, thereby limiting, in a practical sense, the physical depth to which the PDT treatment using hematoporphyrin and PHOTOFRIN.RTM. may be used. BPD-MA has an absorption spectra with peaks in longer wavelength regions, e.g., 690 nm. These compounds are viewed as improvements to the PDT treatment method in that the tissues do not absorb so much of the light energy and therefore allow increased depth of light penetration.
It has been the desire and the practice in PDT treatment to provide uniform illumination in a chosen treatment area.
Allardice et al., Gastrointestinal Endoscopy 35:548-551 (1989) and Rowland et al, PCT application WO 90/00914, disclose a light delivery system designed for use with PDT. The disclosed system involves a flexible tube having a dilator and a transparent treatment window that defines a treatment area by using opaque end-caps made of stainless steel. A fiber optic element that is connected to a laser and ends in a diffusing tip is used in combination with the dilator to deliver light to a tissue source. Allardice et al suggests that the advantages of this apparatus over the use of balloon-type catheter reside in providing a more uniform distribution of light.
Nseyo et al, Urology 36:398-402 (1990) and Lundahl, U.S. Pat. Nos. 4,998,930 and 5,125,925, disclose a balloon catheter device for providing uniform light radiation to the inner walls of hollow organs. The device is a balloon catheter design having a balloon at one end of the apparatus and an optical fiber ending in a diffusion tip that is inserted into the lumen of the balloon through the catheter. The catheter""s centering tube is said to provide a more uniform distribution of the laser light by centering the optical fiber in the inflated balloon. These catheter devices further incorporate optical sensing fibers in the balloon wall to allow measurement of the resulting illumination.
Panjehpour et al, Lasers and Surgery in Medicine 12:631-638 (1992) discloses the use of a centering balloon catheter for esophageal PDT. Panjehpour et al discloses a cylindrical balloon catheter into which a fiber optic probe ending in a light diffuser is inserted.
Overholt et al, Lasers and Surgery in Medicine 14:27-33 (1994) discloses various structures similar to the balloon catheter device described in Panjehpour et al. Overholt et al""s includes a black opaque coating on both ends of the balloon to define a 360xc2x0 treatment window. Overholt et al additionally describes a modified balloon in which one-half of the circumference of the treatment window is rendered opaque to light using the black coating material. This configuration provides a 180xc2x0 treatment window.
Rowland et al, PCT application WO 90/00420, discloses a light-delivery system for irradiating a surface. The device has a hemispherical shell in which the inside is entirely coated with a diffuse reflector. A light source is mounted within the shell. The light source may contain a diffusing source at the tip allowing diffusion of light within the reflective shell.
U.S. Pat. No. 5,344,419, to Spears, discloses devices and methods for making laser-balloon catheters. Spears uses a process that etches an end of a fiber optic cable to provide a diffusion tip on that optical cable. The optical cable containing the etched tip is secured within a central channel of a balloon catheter using a coating of adhesive containing microballoons. The position of the tip within the central channel and the microballoons contained in the adhesive provide increased efficiency in diffusing the laser radiation in a cylindrical pattern, providing uniform illumination at the target site.
U.S. Pat. No. 5,354,293, to Beyer et al, discloses a balloon catheter for delivering light for use in PDT. That balloon catheter employs a conical tipped fiber optic cable for deflecting a light beam radially outward through a transparent portion of an inflated balloon.
Although various of the disclosures discussed above provide ways for providing light to a target site, none of them suggest a procedure for creating lesions in cardiac tissue using PDT, particularly for control of cardiac arrhythymia, nor do they suggest endovascular light-delivery devices that are specifically configured to provide limited lineal or circumferential lesions in cardiac tissue.
This invention relates to methods for producing lesions in cardiac tissue by the step of subjecting cardiac tissue containing a photodynamic drug to a light source in a predetermined pattern to form a lesion corresponding to that predetermined pattern. Normally, the step of forming the lesions is heat-free. The method may also include the step of introducing the photodynarnic drug, locally or systemically, to the cardiac tissue.
Preferably the selected, predetermined pattern is one which limits, controls, or prevents cardiac arrhythymia. Among the preferred predetermined patterns are those which encircle the pulmonary vein bed in the left atrium and those which encircle at least one os of superior pulmonary veins in the left atrium.
The procedure may apply the lesions to the cardiac tissue from the exterior of the heart, e.g., through the epicardium or via a surgical or an endovascular procedure to the interior of the heart.
The preferred light delivery device, i.e., for providing light to the selected cardiac tissue, comprises a generally linear member having a distal region with an axis. That distal region preferably includes a substantially clear and linear light emitting region corresponding to said axis. The light emitting region is preferably bendable to conform to curved cardiac tissue. That light emitting region generally emits all of the light emanating from said device and may be, e.g., a window or lens or at least one LED.